As a group of enzymes produced intracellularly, cathepsin series proteases (cathepsin B, cathepsin L, cathepsin H, etc.) are discharging a variety of physiological functions both intracellularly and extracellularly. For example, it is thought that intracellularly those enzymes are involved in the processing of proteins, decomposition of unwanted proteins, and apoptosis, while extracellularly they are associated with the decomposition of extracellular matrices such as degradation of bone matrix collagen and digestion of infecting bacteria.
Cathepsin L, in particular, is known to have very strong collagen degrading activity and it has been demonstrated in experimental animals, too, that inhibitors of cathepsin L exhibit marked inhibitory effects on the decomposition of bone collagen. Any substance that inhibits cathepsin L specifically is considered to be a promising drug for the therapy of osteoporosis (FEBS Letters, 269 (1), 189-193, 1990). Moreover, such a specific inhibitor of cathepsin L is considered to be a promising drug for the therapy of hypercalcemia.
Cathepsin B is an enzyme which is said to be etiologically associated, in a large measure, with inflammations, cancer metastases, myodystrophy and the like. Recent years have witnessed an increasing number of reports pointing out the correlation between the malignancy of cancer, such as metastasis and invasion, and cathepsin B activity (Cancer Research, 52, 3610-3614, 1992).
For treating diseases associated with cathepsin series proteases, specific inhibitors of those enzymes are needed today but no satisfactory substance has been discovered as yet. Particularly, there is not available a specific inhibitor of the cathepsin associated with bone resorption in osteoporosis.
The present invention has for its object to produce a substance having excellent cathepsin inhibitory activity by utilizing microorganisms.